Neurological disease is recognized prior to overt acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1 (HIV) infection. The mechanism of early neurologic injury needs study to address basic questions of neuro-AIDS pathogenesis. Whether neurological deficits seen in AIDS is due to cumulative injury beginning in the pre-AIDS phase, or whether separate mechanisms are activated at later infection stages can only be determined when the mechanisms active during pre-AIDS infection are known. Clinical development of FIV infection closely models HIV disease. The project hypothesis is Persistent alterations in gene regulation in the brain cause progressive neuronal injury during the asymptomatic phase of FIV infection of the cat. Three specific aims will (1) study the kinetics of neuronal loss in pre-AIDS phase FIV infection with unbiased stereological methods, (2) use quantitative polymerase chain reaction (PCR) to show brain viral load is constantly low in this phase, and (3) identify differentially expressed genes between infected and uninfected cats using differential display PCR. The altered gene expression detected will not only help define the molecular mechanisms for the pre-AIDS stage of lentiviral nervous system disease, but will also provide a basis for future study differentiating those mechanisms activated only in the AIDS stage of infection. If neuronal loss is proven to occur during pre-AIDS, these mechanisms will require understanding so that early intervention may occur.